The pharmacokinetics and electroencephalogram response of remifentanil alone and in combination with esmolol in the rat.
OBJECTIVE
The goal of this study was to determine if the co-administration of esmolol (ES), a short acting cardioselective beta-blocker, significantly alters the pharmacokinetics and/or pharmacodynamics of remifentanil (REMI), an ultra short-acting opioid, in the rat.


METHODS
Sprague-Dawley rats (N = 8, Wt. = 325 +/- 15 g) were surgically implanted with stainless steel cerebrocortical EEG electrodes three days before the study. Each rat was dosed with REMI (15 micrograms/kg/min), and REMI & ES (15 micrograms/kg/min and 600 micrograms/kg/min) for 21 minutes in a random crossover design. Six serial blood samples were collected over 25 minutes into test-tubes containing 0.5 ml acetonitrile. Blood samples were extracted with methylene chloride and analyzed by a validated GC-MS assay. EEG was captured and subjected to power spectral analysis (0.1-50 Hz) for spectral edge (97%).


RESULTS
No significant differences (p < 0.05) were found in clearance (REMI = 287 + 73 ml/min/leg vs. REMI & ES = 289 +/- 148 ml/min kg) or Vd (REMI = 286 +/- 49 ml/kg vs REMI & ES = 248 + 40 ml/kg). A linked sigmoid Emax PK-PD model was used and the pharmacodynamic parameters were not statistically different. Mean Emax and EC50 after REMI were 18.0 +/- 6.0 Hz and 32 +/- 12 ng/ml; and after REMI + ES were 19 + 4.8 Hz and 26 + 8.6 ng/ml.


CONCLUSIONS
At the doses tested, there is no pharmacokinetic or pharmacodynamic interaction between remifentanil and esmolol in the rat.
Haidar
S H
SH
Pharmacokinetics-Biopharmaceutics Laboratory, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
Moreton
J E
JE
Liang
Z
Z
Hoke
J F
JF
Muir
K T
KT
Eddington
N D
ND
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D018592:Cross-Over Studies; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects*; D006207:Half-Life; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil
D000319:Adrenergic beta-Antagonists; D000701:Analgesics, Opioid; D010880:Piperidines; D011412:Propanolamines; C036604:esmolol; D000077208:Remifentanil